Myriad Genetics

537 Background: Biomarkers do not yet exist to triage patients with oligometastatic ccRCC for de-escalation strategies. Two promising biomarkers are kidney injury molecule-1 (KIM-1) and circulating tumor DNA (ctDNA). Methods: Patients with ccRCC and ≤5 metastases were enrolled on a single-arm phase 2 trial of metastasis-directed therapy (MDT) without systemic therapy (NCT03575611), powered for the primary endpoint of systemic therapy–free survival (STFS). Plasma samples for ctDNA and KIM-1 measurement were collected at baseline and 3-month follow-up. Personalized ctDNA detection panels (≤2000 somatic variants) were constructed from tumor whole-genome sequencing (Myriad Genetics). To create the Kidney Cancer OligoMetastasis Prognostic Assessment Systemic Score (K-COMPASS), we screened 24 candidate variables by elastic net-penalized Cox regression with 5-fold cross-validation repeated 100 times, with performance assessed by C-index. Predictors with nonzero coefficients were refit with Weibull regression for STFS. Results: Among 112 patients with KIM-1 measurements available, median baseline KIM-1 level was 127.0 pg/mL (IQR 71.5–228.0). KIM-1 and ctDNA were associated with STFS at baseline and 3 months in univariable and multivariable analyses (table). Progression-free survival (PFS) and overall survival (OS) were also associated with KIM-1 at baseline (PFS: HR=2.2, 95% CI 1.5–3.3; OS: HR=5.1, 95% CI 2.5–10.2, P <0.001) and at 3 months (PFS: HR=3.5, 95% CI 2.2–5.5; OS: HR=5.0, 95% CI 2.3–10.9) (all P <0.001). K-COMPASS construction selected baseline KIM-1, baseline ctDNA MRD, and 4 clinical variables (prior systemic therapy lines, ECOG performance status, number of metastatic lesions, time from diagnosis to metastasis). The complete model showed strong discrimination (C-index=0.76) and excellent calibration (slope=1). A user-facing K-COMPASS tool is available online (www.trialdesign.org). Conclusions: To our knowledge, this is the first evaluation of KIM-1 in oligometastatic ccRCC and the first to analyze KIM-1 and ctDNA in tandem for RCC. Both biomarkers were strongly and independently associated with outcomes in patients receiving MDT without systemic therapy. Integrating KIM-1 and ctDNA with clinical factors (K-COMPASS) yielded a well-calibrated model with high discrimination to support risk-adapted decision-making. External validation is planned. Univariable and multivariable association of baseline KIM-1 and ctDNA MRD status with systemic therapy free survival. HR (95% CI) Baseline 3-Month Follow-Up Univariable Multivariable Univariable Multivariable KIM-1(per log10[pg/mL]) 2.5 (1.5–4.1) P <0.001 1.9 (1.0–3.6) P =0.041 3.2 (1.9–5.4) P< 0.001 2.2 (1.1–4.5) P =0.028 ctDNA (MRD+ vs MRD–) 2.8 (1.3–5.9) P =0.0089 2.5 (1.1–5.6) P =0.032 4.4 (2.1–9.5) P< 0.001 2.7 (1.1–6.7) P =0.032

Efficient workload forecasting is a key enabler of modern AIOps (Artificial Intelligence for IT Operations), supporting proactive and autonomous resource management across the computing continuum, from edge environments to large-scale cloud infrastructures. In this paper, we propose a Temporal Transformer architecture for CPU utilization prediction, designed to capture both short-term fluctuations and long-range temporal dependencies in workload dynamics. The model is first pretrained on a large-scale Microsoft Azure VM dataset and subsequently fine-tuned on the Alibaba container dataset, enabling effective transfer learning across heterogeneous virtualization environments. Experimental results demonstrate that the proposed approach achieves high predictive accuracy while maintaining a compact model size and inference times compatible with real-time operation. Qualitative analyses further highlight the model’s ability to reproduce workload patterns with high fidelity. These findings indicate that the proposed Temporal Transformer constitutes a lightweight and accurate forecasting component for next-generation AIOps pipelines, suitable for deployment across both cloud and edge intelligence scenarios.

1073 Background: The combination of CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) is the standard first-line treatment for patients with hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (MBC). However, it exhibits highly variable efficacy, with some cancers progressing within 3–6 months while many others achieve durable and potentially indefinite complete responses (CRs). While pharmacologic strategies to escalate or deescalate this therapy exist, diagnostic tools to identify the patients who would benefit from each approach are needed. Ultrasenstive ctDNA offers the potential to assess disease burden dynamically and with more precision. In this study, we evaluate the validity of an ultrasensitive assay capable of detecting ctDNA levels in the parts per million range for monitoring patients with HR+/HER2- MBC. Methods: Patients from the MSK-LINC prospective ctDNA monitoring study, who received CDK4/6i+ET for HR+/HER2- MBC were included in the study. MRD monitoring was performed using personalized tumor-informed panels designed from whole genome sequencing (WGS) of matched tumor and normal specimens to identify up to 2,000 somatic alterations for each patient using the Precise MRD assay (Myriad Genetics). Results were reported as an overall ctDNA detection status and a quantitative tumor fraction. Results: 29 patients with HR+/HER2- MBC (8 de novo , 21 recurrent) were included in this ongoing study. The median progression-free survival (PFS) was 48.8 months (range 2.6 – 78.5) with 17/29 of patients experiencing disease progression. ctDNA panels were successfully designed for all cases, and 140/146 (95.9%) plasma samples passed QC. All pre-treatment samples had detectable ctDNA with a median tumor fraction of 1.4% (range 0.00093%, 14.0%). An early decrease in ctDNA levels, > 50% reduction from baseline or levels < 0.01% in the second sample collected within 3 months, was significantly associated with longer PFS (p < 0.001). We focused on 7 patients who achieved radiographic CR all with PFS > 3y. Notably, 3 patients had continued to have ultra low levels of ctDNA (median: 0.0086%, range 0.00032%, 0.11%), indicating stable viable micrometastatic disease below the threshold of imaging, effectively controlled by treatment. In contrast, 4 patients also achieved molecular CR (mCR) defined as sustained undetectable ctDNA suggesting that metastatic disease was either eradicated or rendered dormant without significant cell turnover. Conclusions: Ultrasensitive ctDNA monitoring is a promising tool for monitoring disease burden and treatment response. Our results highlight the ability of ctDNA to distinguish between stable molecular disease vs. mCR, highlighting the potential of ctDNA as a biomarker for tailoring treatment strategies in patients who achieve outstanding clinical responses.

Abstract Background: Current treatment for frontline ccRCC focuses on systemic therapy doublets. Although effective, such combinations exhibit substantial toxicities and healthcare costs. An underutilized option is MRWS, which may facilitate a prolonged systemic therapy-free interval in select patients. Unfortunately, no reliable prognostic markers exist to select patients for MRWS. Although ctDNA assays may guide patient selection, implementation in ccRCC has proven challenging due to limited ctDNA shedding. Therefore, advanced sequencing and bioinformatic pipelines are needed to enhance ctDNA reliability in ccRCC. Methods: This phase 2 single-arm trial (NCT03575611) enrolled patients with oligometastatic ccRCC and up to 5 metastases. All patients had either never received systemic therapy or ceased >1 month earlier. Patients were treated with MRWS, consisting of predominately stereotactic radiation therapy to all sites of disease. Subsequent rounds of MRWS were administered if limited progression was observed. The co-primary endpoints were progression free survival (PFS) and systemic therapy free survival (STFS). For the latter, a median STFS of >24 months (mo) was prespecified as the threshold for success. Individualized ctDNA panels (Myriad Genetics) were created from tumor whole genome sequencing and applied to serial plasma samples. Molecular residual disease (MRD) status was determined based on whether ctDNA was detected (MRD+) or not (MRD-). Results: Between July 2018 to May 2023, 121 oligometastatic ccRCC patients were enrolled. Median follow up was 36 mo (range 13-68 mo). Most patients (72%) had 1 site of metastatic disease and had never received systemic therapy (70%). The median PFS was 18 mo (95% CI: 15-22 mo) and STFS was 34 mo (95% CI: 28-54 mo). The lower bounds of 95% CI of the median STFS exceeded the prespecified 24 mo threshold for success. Two-year PFS and STFS were 40% and 75%, respectively. Median OS was not reached, and 2- and 3-year OS were 94% and 87%, respectively. Eight (7%) patients experienced grade 3+ toxicities at least possibly attributed to MRWS. There were no grade 5 toxicities.MRD+ was detected in 56% of patients at baseline and associated with significantly shorter STFS (HR 2.9, 95% CI 1.4-6.1, P=0.003). Patients who were MRD+ and MRD- at baseline exhibited 27 vs. 54 mo median STFS, respectively. Three months after MRWS, 31% of MRD + patients converted to MRD-. Positive MRD status at 3 month follow up was strongly associated with shorter STFS (HR 4.3, 95% CI 2.0-9.0, P<0.001). Conclusions: MRWS exhibited excellent tolerability and facilitated prolonged time off systemic therapy without compromising OS. Our ctDNA approach appears to be a promising baseline prognostic biomarker for STFS and a dynamic marker of MRWS response. Citation Format: Chad Tang, Alexander Sherry, Aaron Seo, Kieko Hara, Haesun Choi, Suyu Liu, Xiaowen Sun, Anya Montoya, Ethan Ludmir, Amishi Y. Shah, Eric Jonasch, Amado J. Zurita, Craig Kovitz, Christopher J. Battey, Sarah Ratzel, Giannicola Genovese, Kanishka Sircar, Jose Karam, Nizar Tannir, Pavlos Msaouel. Phase 2 trial of metastasis directed radiotherapy without systemic therapy (MRWS) for oligometastatic clear cell renal cell carcinoma (ccRCC) and investigation of circulating tumor DNA (ctDNA) as a personalized biomarker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT132.

Abstract — Each bank with its own advantages can choose its own development strategy. In My Tho city, Tien Giang province, the demand for consumer loans is increasing sharply for daily consumption purposes. Meeting this demand not only helps the bank attract but also increases customer satisfaction and loyalty. However, consumer credit activities at BIDV My Tho have not been effective. The study was conducted to analyze, evaluate and propose solutions to develop consumer credit at BIDV My Tho until 2026 such as: Diversifying and developing new products, having policies to attract customers, modernizing banking technology and improving the quality of bank staff.

Fragility fractures are still a worldwide health burden in the context of population aging. In particular, the global number of hip fractures is expected to double between 2020 and 2050. Therefore, it is essential to detect patients at risk of fragility fracture at the population scale. The current golden standard is dual X-ray absorptiometry (DXA), providing the areal bone mineral density (aBMD). Ultrasonic devices, usually more portable and cheaper than X-ray devices, represent interesting DXA alternatives as screening tools. However, operator dependency is usually recognized as their main drawback. In this study, the measurement protocol of the bi-directional axial transmission (BDAT) ultrasonic device is presented in detail. The dedicated ultrasonic probe is placed at the one-third distal radius of the non-dominant forearm using conventional coupling gel. The guided interface provides in quasi-real time (about 2 Hz) four parameters of interest: velocities of the first arriving signal (vFAS) and the A0 mode (vA0),cortical thickness (Ct.Th) and porosity (Ct.Po), as well as four quality parameters. The operator moves the probe slowly at the measurement site, carefully observing the feedback provided by the interface until finding a stable position and starting a series of 10 acquisitions. When at least four consistent series are obtained, the measurement ends, and an automatic report is generated. The measurement usually takes about 5 min to complete. To determine the robustness of this protocol, a reproducibility study was conducted among 3 operators (one expert and two novices) and 14 healthy participants (6 women, 8 men, 21-53 years old). The intraclass correlation coefficients (ICC) were found good for vA0 (0.76), Ct.Po (0.80) or excellent for Ct.Th (0.87) and vFAS (0.91). The standard deviations were found to be less than 10% of the total ranges in clinical practice.